Identification of a major keratinocyte cell envelope protein, loricrin

Mehrel, Thomas; Hohl, Daniel; Rothnagel, Joseph A.; Longley, Mary A.; Bundman, Donnie S.; Cheng, Christina; Lichti, Ulrike; Bisher, M. E.; Steven, Alasdair C.; Steinert, Peter M.; Yuspa, Stuart H.; Roop, Dennis R.

doi:10.1016/0092-8674(90)90073-n

Cited by 409 publications

(351 citation statements)

References 51 publications

Supporting

Mentioning

339

Contrasting

Unclassified

Order By: Relevance

“…2 J). Loricrin and filaggrin, which are markers for late stages of terminal differentiation and normally expressed in the granular layer of the epidermis (25,26), did not appear to be altered in the ML.⌬␤RII epidermis (data not shown).…”

Section: Ml⌬␤rii Transgenic Mice Exhibit a Hyperplastic͞mentioning

confidence: 96%

Expression of a dominant-negative type II transforming growth factor β (TGF-β) receptor in the epidermis of transgenic mice blocks TGF-β-mediated growth inhibition

Wang

Greenhalgh

Bickenbach

et al. 1997

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

133

125

View full text Add to dashboard Cite

To determine whether a functional type II receptor of transforming growth factor ␤ (TGF-␤) is required to mediate the growth inhibitory effect of TGF-␤ on the skin in vivo, we have generated transgenic mice that overexpress a dominant negative-type II TGF-␤ receptor (⌬␤RII) in the epidermis. The ⌬␤RII mice exhibited a thickened and wrinkled skin, and histologically the epidermis was markedly hyperplastic and hyperkeratotic. In vivo labeling with BrdUrd showed a 2.5-fold increase in the labeling index over controls, with labeled nuclei occurring in both basal and suprabasal cells of transgenic epidermis. In heterozygotes, this skin phenotype gradually diminished, and by 10-14 days after birth the transgenic mice were indistinguishable from their normal siblings. However, when F 1 mice were mated to homozygosity, perinatal lethality occurred due to the severe hyperkeratotic phenotype, which restricted movement. Cultured primary keratinocytes from ⌬␤RII mice also exhibited an increased rate of growth in comparison with nontransgenic controls, and were resistant to TGF-␤-induced growth inhibition. These data document the role of the type II TGF-␤ receptor in mediating TGF-␤-induced growth inhibition of the epidermis in vivo and in maintenance of epidermal homeostasis.

show abstract

Section: Ml⌬␤rii Transgenic Mice Exhibit a Hyperplastic͞mentioning

confidence: 96%

Expression of a dominant-negative type II transforming growth factor β (TGF-β) receptor in the epidermis of transgenic mice blocks TGF-β-mediated growth inhibition

Wang

Greenhalgh

Bickenbach

et al. 1997

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

133

125

View full text Add to dashboard Cite

show abstract

“…Transcripts encoding K1 and K10 are subsequently down-regulated in the granular layer, where the late marker genes loricrin and ®laggrin are induced (Roop et al, 1988;Fuchs, 1990). In addition, keratinocyte transglutaminases are activated in the granular layer to catalyze the formation of corni®ed envelopes (reviewed in Polakowska and Goldsmith, 1991), insoluble structures composed of precursor proteins involucrin (Rice and Green, 1979), small proline rich (spr) proteins (Kartasova et al, 1987;Marvin et al, 1992), loricrin (Mehrel et al, 1990), and other components (Steinert and Merekov, 1995).…”

Section: Introductionmentioning

confidence: 99%

Opposing activities of c-Fos and Fra-2 on AP-1 regulated transcriptional activity in mouse keratinocytes induced to differentiate by calcium and phorbol esters

Rutberg

Sáez

et al. 1997

Oncogene

View full text Add to dashboard Cite

The major di erentiation products of maturing keratinocytes contain AP-1 regulatory motifs, and AP-1 DNA binding activity increases in cultured keratinocytes induced to di erentiate by calcium. Here, we have analysed AP-1 transcriptional activity in mouse keratinocytes treated with calcium and 12-O-tetradecanoyl phorbol-13-acetate (TPA), two agents that induce terminal di erentiation of keratinocytes with di erent phenotypic consequences. Reporter constructs representing multimers of AP-1 sequences found in keratinocyte marker genes demonstrated that the calcium-induced AP-1 DNA binding activity does not correlate with transcriptional activation. Moreover, expression from active subunits of the pro®laggrin and spr 1 promoters increased in calcium-treated keratinocytes when the AP-1 sites were disrupted, indicating that AP-1 may negatively regulate certain promoters in these cells. In contrast, AP-1 reporter activity was increased in keratinocytes treated with TPA. This induction was dependent upon the expression of c-Fos since AP-1 transcriptional activity was not increased in TPA-treated keratinocytes derived from c-fos null mice. Analysis of AP-1 protein expression in calcium-and TPA-treated keratinocytes demonstrated that only TPA increased the expression of c-Jun, while Jun B and Jun D were induced by both of these agents. c-Fos was expressed only in TPA treated keratinocytes, Fra-2 was expressed only in calcium-treated cells, and Fra-1 was expressed in both. Exogenous expression of Fra-2 repressed AP-1 transcriptional activity in TPA-treated keratinocytes, while c-Fos expression activated the AP-1 sequence in calcium-treated keratinocytes. These data indicate that Fra-2 and c-Fos play opposing roles in regulating AP-1 activity in keratinocytes and that multiple inducerdependent regulatory pathways may exist for the expression of keratinocyte di erentiation markers.

show abstract

“…Terminal differentiation, occurring in the granular compartment, is characterized by flattening of cells, enucleation and finally cell death leading to sloughing of the cells off the skin surface. This process is associated with the induced expression of loricrin, filaggrin and other proteins (Fuchs and Raghavan, 2002;Mehrel et al, 1990).…”

Section: The Involvement Of the Irs Proteins In Epidermal Proliferatimentioning

confidence: 99%

Insulin receptor substrate 1 (IRS‐1) plays a unique role in normal epidermal physiology

Sadagurski

Nofech‐Mozes

Weingarten

et al. 2007

Journal Cellular Physiology

View full text Add to dashboard Cite

Insulin receptor substrate (IRS) proteins play a central role in insulin signaling. Previously we have demonstrated that insulin is essential for normal skin development and function. In the present study we investigated the involvement of the IRS-1 and IRS-2 proteins in skin physiology and in mediating insulin action in skin. For this purpose we have investigated the effects of inactivation of each of the IRSs on skin, studying skin sections and primary skin cells derived from IRS-1 or IRS-2 null mice. We have demonstrated that while the skin of the IRS-2 null mice appeared normal, the skin of the IRS-1 null mice was thinner and translucent. Histological analysis revealed that the thinning of the IRS-1 null skin was a consequence of the thinning of the spinous compartment, consisting of fewer layers. Proliferation of the IRS-1 and IRS-2 null skin epidermal cells was normal. However, the differentiation process of the IRS-1 skin and skin cells was impaired. There was a marked decrease in the induction of the expression of K1, the marker of advanced stages of skin differentiation. In contrary, IRS-2 inactivation had no effects on skin differentiation. In conclusion, we have shown for the first time that IRS-1 but not IRS-2 has an effect on skin formation and development, being one of the main activators of the differentiation process in skin keratinocytes. Furthermore, we suggest that IRS-1 and IRS-2 have distinct roles in skin physiology.

show abstract

Identification of a major keratinocyte cell envelope protein, loricrin

Cited by 409 publications

References 51 publications

Expression of a dominant-negative type II transforming growth factor β (TGF-β) receptor in the epidermis of transgenic mice blocks TGF-β-mediated growth inhibition

Expression of a dominant-negative type II transforming growth factor β (TGF-β) receptor in the epidermis of transgenic mice blocks TGF-β-mediated growth inhibition

Opposing activities of c-Fos and Fra-2 on AP-1 regulated transcriptional activity in mouse keratinocytes induced to differentiate by calcium and phorbol esters

Insulin receptor substrate 1 (IRS‐1) plays a unique role in normal epidermal physiology

Contact Info

Product

Resources

About